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1.
Vitamin D Supplementation in Patients with Juvenile Idiopathic Arthritis.
Wu, CY, Yang, HY, Luo, SF, Huang, JL, Lai, JH
Nutrients. 2022;(8)
Abstract
Vitamin D has been implicated in the pathogenesis of skeletal disorders and various autoimmune disorders. Vitamin D can be consumed from the diet or synthesized in the skin upon ultraviolet exposure and hydroxylation in the liver and kidneys. In its bioactive form, vitamin D exerts a potent immunomodulatory effect and is important for bone health. Juvenile idiopathic arthritis (JIA) is a collection of inflammatory joint diseases in children that share the manifestation of inflamed synovium, which can result in growth arrest, articular deformity, bone density loss, and disability. To evaluate the potential effect of vitamin D on JIA disease manifestations and outcomes, we review the role of vitamin D in bone metabolism, discuss the mechanism of vitamin D in modulating the innate and adaptive immune systems, evaluate the clinical significance of vitamin D in patients with JIA, and summarize the supplementation studies.
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2.
Association of External Ventricular Drain Wean Strategy with Shunt Placement and Length of Stay in Subarachnoid Hemorrhage: A Prospective Multicenter Study.
Chung, DY, Thompson, BB, Kumar, MA, Mahta, A, Rao, SS, Lai, JH, Tadevosyan, A, Kessler, K, Locascio, JJ, Patel, AB, et al
Neurocritical care. 2022;(2):536-545
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Abstract
BACKGROUND Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.
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Ferroptosis and Autoimmune Diseases.
Lai, B, Wu, CH, Wu, CY, Luo, SF, Lai, JH
Frontiers in immunology. 2022;:916664
Abstract
Adequate control of autoimmune diseases with an unclear etiology resulting from autoreactivation of the immune system remains a major challenge. One of the factors that trigger autoimmunity is the abnormal induction of cell death and the inadequate clearance of dead cells that leads to the exposure or release of intracellular contents that activate the immune system. Different from other cell death subtypes, such as apoptosis, necroptosis, autophagy, and pyroptosis, ferroptosis has a unique association with the cellular iron load (but not the loads of other metals) and preserves its distinguishable morphological, biological, and genetic features. This review addresses how ferroptosis is initiated and how it contributes to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases. The mechanisms responsible for ferroptosis-associated events are discussed. We also cover the perspective of targeting ferroptosis as a potential therapeutic for patients with autoimmune diseases. Collectively, this review provides up-to-date knowledge regarding how ferroptosis occurs and its significance in autoimmune diseases.
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[Modified posteromedial approach via lateral side of flexor hallucis longus for the treatment of posterior Pilon fracture].
Lai, ZB, Zhu, YZ, Zou, YX, Zhang, HN, Li, X, Zhong, DG, Yang, KY, Lai, JH, Shen, GD
Zhonghua yi xue za zhi. 2021;(15):1077-1082
Abstract
Objective: To compare the clinical efficacy and the level of muscle and soft tissue damage between modified posteromedial approach via lateral side of flexor hallucis longus and modified posteromedial approach in the treatment of posterior Pilon fracture. Methods: Total of 43 patients (27 males and 16 females, aged from 19 to 71 years) diagnosed with posterior Pilon fracture from June 2016 to June 2018 in Foshan Hospital of Traditional Chinese Medicine were randomly divided into observation group (modified posteromedial approach via lateral side of flexor hallucis longus, 21 cases) and control group (modified posteromedial approach, 22 cases) according to the operation approach. The preoperative waiting time, intraoperative time, intraoperative blood loss, hospitalization time and the complications were recorded and compared between the two groups. The differences of blood creatine kinase (CK), myoglobin (Myo) and C-reactive protein (CRP) at different time points before and after operation were compared between the two groups to elevate the level of muscle and soft tissue damage. The fracture reduction qualities of the two groups were compared by Burwell-Charnley criteria. The differences of fracture healing time, range of motion of metatarsophalangeal joint of the great toe (MTP-ROM), ankle range of motion (Ankle-ROM), American Orthopaedic Foot & Ankle Society (AOFAS) score and visual analogue scale (VAS) score of pain were compared between the two groups at the last follow-up. Results: The observation group and the control group were followed-up for (19±6) months and (16±8) months, respectively; there was no significant difference between the two groups (P>0.05). There were no significant differences in preoperative waiting time, intraoperative blood loss, hospitalization time and fracture healing time between the two groups (all P>0.05). At the last follow-up, there was no significant difference in the MTP-ROM and Ankle-ROM between the two groups (both P>0.05); the AOFAS score of the observation group was 88.2±7.8 and it was 84.5±7.6 in the control group (P>0.05); the VAS score of the observation group was (0.9±1.0) and it was (1.3±0.8) in the control group(P>0.05). Anatomical reduction rate in observation group was higher than that in control group (90.5% vs 81.8%, P>0.05). The operation time in the observation group was (87±16) min and it was (98±11) min in the control group (P<0.05). CK, Myo and CRP were increased in both groups after surgery, but there was no statistical significance between groups at the same time point (all P>0.05). There was no nerve injury in the observation group, while 2 cases (9.0%) of nerve paralysis occurred in the control group. No incision infection and checkrein deformity of the Hallux was found in the two groups. Conclusion: The modified posteromedial approach via lateral side of flexor hallucis longus can obtain good operative field exposure, and does not increase muscle and soft tissue injury, with shorter operative time and fewer complications, without nerve injury and checkrein deformity, it is a safe approach for the treatment of posterior Pilon fracture.
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Low-intensity elbow flexion eccentric contractions attenuate maximal eccentric exercise-induced muscle damage of the contralateral arm.
Chen, TC, Lin, MJ, Lai, JH, Chen, HL, Yu, HI, Nosaka, K
Journal of science and medicine in sport. 2018;(10):1068-1072
Abstract
OBJECTIVES The magnitude of muscle damage induced by maximal eccentric contractions (MaxEC) of the elbow flexors (EF) is reduced when it is preceded by low-intensity (10% of maximal voluntary isometric contraction strength) eccentric contractions (10%EC) of the same muscle, or by MaxEC of the opposite EF. This study investigated whether 10%EC would reduce the magnitude of muscle damage after MaxEC performed by the opposite arm. DESIGN Comparison among 6 groups for changes in indirect markers of muscle damage. METHOD Young (21.0±1.8years) untrained men were assigned to five experimental groups (n=13/group) that performed 30, 10%EC followed by 30 MaxEC of the other arm performed at either 1 (1d), 2 (2d), 7 (1wk), 14 (2wk) or 21days (3wk) later, and one control group that performed 30 MaxEC without 10%EC (n=13). Changes in several indirect markers of muscle damage after MaxEC were compared among the groups by mixed-design two-way ANOVAs. RESULTS No significant changes in maximal voluntary concentric contraction torque, plasma creatine kinase activity and muscle soreness were evident after 10%EC. Changes in these variables after MaxEC were smaller (p<0.05) for the 1d, 2d and 1wk groups than control group, without significant differences between the 1d, 2d and 1wk groups. No significance differences in the changes were evident among the 2wk, 3wk and control groups, except for muscle soreness showing smaller (p<0.05) increases for the 2wk and 3wk groups than control group. CONCLUSIONS These results showed that 10%EC conferred muscle damage protection to the contralateral arm that performed MaxEC.
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Muscle damage protective effect by two maximal isometric contractions on maximal eccentric exercise of the elbow flexors of the contralateral arm.
Chen, TC, Lin, MJ, Chen, HL, Lai, JH, Yu, HI, Nosaka, K
Scandinavian journal of medicine & science in sports. 2018;(4):1354-1360
Abstract
Muscle damage after 30 maximal eccentric contractions of the elbow flexors (30MVEC) is reduced when the same exercise is performed by the opposite arm, and when two maximal voluntary isometric contractions at a long muscle length (2MVIC) are performed prior to 30MVEC by the same arm. This study investigated the hypothesis that 2MVIC would attenuate muscle damage after 30MVEC performed by the opposite arm. Untrained young (20-25 years) men were placed into 1 of 4 experimental groups that performed 2MVIC at 1 (1d), 2 (2d), 4 (4d), or 7 days (7d) before 30MVEC by the opposite arm, or one control group that performed 30MVEC only (n = 13/group). Changes in indirect muscle damage markers after 30MVEC were compared among the groups by mixed-design two-way ANOVA. Maximal voluntary concentric contraction torque, range of motion, plasma creatine kinase activity, and muscle soreness did not change significantly after 2MVIC. Changes in these variables after 30MVEC were smaller (P < .05) for 1d (eg, peak soreness: 45 ± 21 mm) and 2d groups (46 ± 20 mm) than control group (66 ± 18 mm), without significant differences between 1d and 2d groups. No significant differences in the changes were found among 4d, 7d, and control groups, except for soreness showing smaller (P < .05) increases for 4d group (54 ± 19 mm) than 7d (62 ± 17 mm) and control groups. These results supported the hypothesis and showed that muscle damage induced by 30MVEC was reduced by 2MVIC performed 1-2 days prior to 30MVIC by the contralateral arm.
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7.
Sphingosine kinase 1 isoform-specific interactions in breast cancer.
Yagoub, D, Wilkins, MR, Lay, AJ, Kaczorowski, DC, Hatoum, D, Bajan, S, Hutvagner, G, Lai, JH, Wu, W, Martiniello-Wilks, R, et al
Molecular endocrinology (Baltimore, Md.). 2014;(11):1899-915
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Abstract
Sphingosine kinase 1 (SK1) is a signaling enzyme that catalyzes the formation of sphingosine-1-phosphate. Overexpression of SK1 is causally associated with breast cancer progression and resistance to therapy. SK1 inhibitors are currently being investigated as promising breast cancer therapies. Two major transcriptional isoforms, SK143 kDa and SK151 kDa, have been identified; however, the 51 kDa variant is predominant in breast cancer cells. No studies have investigated the protein-protein interactions of the 51 kDa isoform and whether the two SK1 isoforms differ significantly in their interactions. Seeking an understanding of the regulation and role of SK1, we used a triple-labeling stable isotope labeling by amino acids in cell culture-based approach to identify SK1-interacting proteins common and unique to both isoforms. Of approximately 850 quantified proteins in SK1 immunoprecipitates, a high-confidence list of 30 protein interactions with each SK1 isoform was generated via a meta-analysis of multiple experimental replicates. Many of the novel identified SK1 interaction partners such as supervillin, drebrin, and the myristoylated alanine-rich C-kinase substrate-related protein supported and highlighted previously implicated roles of SK1 in breast cancer cell migration, adhesion, and cytoskeletal remodeling. Of these interactions, several were found to be exclusive to the 43 kDa isoform of SK1, including the protein phosphatase 2A, a previously identified SK1-interacting protein. Other proteins such as allograft inflammatory factor 1-like protein, the latent-transforming growth factor β-binding protein, and dipeptidyl peptidase 2 were found to associate exclusively with the 51 kDa isoform of SK1. In this report, we have identified common and isoform-specific SK1-interacting partners that provide insight into the molecular mechanisms that drive SK1-mediated oncogenicity.